scholarly journals Menin: a scaffold protein that controls gene expression and cell signaling

2013 ◽  
Vol 38 (8) ◽  
pp. 394-402 ◽  
Author(s):  
Smita Matkar ◽  
Austin Thiel ◽  
Xianxin Hua
Keyword(s):  
Gene Expression ◽  
Cell Signaling ◽  
Scaffold Protein

scholarly journals Nanoconfinement of Microvilli Alters Gene Expression and Boosts T cell Activation

2021 ◽  
Author(s):  
Morteza Aramesh ◽  
Diana Stoycheva ◽  
Ioana Sandu ◽  
Stephan J. Ihle ◽  
Tamara Zund ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
T Cell ◽  
Cell Signaling ◽  
T Cell Activation ◽  
Cell Activation ◽  
Local Environment ◽  
T Cell Signaling ◽  
Sense And Respond ◽  
Altered Gene

T cells sense and respond to their local environment at the nanoscale by forming small actin-rich protrusions, called microvilli, which play critical roles in signaling and antigen recognition, particularly at the interface with the antigen presenting cells. However, the mechanisms by which microvilli contribute to cell signaling and activation is largely unknown. Here, we present a tunable engineered system that promotes microvilli formation and T cell signaling via physical stimuli. We discovered that nanoporous surfaces favored microvilli formation, and markedly altered gene expression in T cells and promoted their activation. Mechanistically, confinement of microvilli inside of nanopores leads to size-dependent sorting of membrane-anchored proteins, specifically segregating CD45 phosphatases and T cell receptors (TCR) from the tip of the protrusions when microvilli are confined in 200 nm pores, but not in 400 nm pores. Consequently, formation of TCR nanoclustered hotspots within 200 nm pores, allows sustained and augmented signaling that prompts T cell activation even in the absence of TCR agonists. The synergistic combination of mechanical and biochemical signals on porous surfaces presents a straightforward strategy to investigate the role of microvilli in T cell signaling as well as to boost T cell activation and expansion for application in the growing field of adoptive immunotherapy.

Effect of particulate matter 2.5 on gene expression profile and cell signaling in JEG-3 human placenta cells

2018 ◽  
Vol 33 (11) ◽  
pp. 1123-1134 ◽  
Author(s):  
Woong Kim ◽  
Yoon Cho ◽  
Mi-Kyung Song ◽  
Jung-hee Lim ◽  
Jin young Kim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Particulate Matter ◽  
Cell Signaling ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Human Placenta ◽  
Particulate Matter 2.5

Vitamin E Mediates Cell Signaling and Regulation of Gene Expression

2004 ◽  
Vol 1031 (1) ◽  
pp. 86-95 ◽  
Author(s):  
ANGELO AZZI ◽  
RENÉ GYSIN ◽  
PETRA KEMPNÁ ◽  
ADELINA MUNTEANU ◽  
YESIM NEGIS ◽  
...  
Keyword(s):  
Gene Expression ◽  
Vitamin E ◽  
Cell Signaling ◽  
Regulation Of Gene Expression

Microarray Analysis of Peripheral Blood Monocytes in Sickle Cell Anemia Patients with Cerebrovascular Stenosis.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3570-3570
Author(s):  
M. Catherine Driscoll ◽  
Remi Adenika ◽  
Ronald L. Nagel ◽  
Eric P. Hoffman
Keyword(s):  
Gene Expression ◽  
Cell Signaling ◽  
Differentially Expressed Genes ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Peripheral Blood ◽  
Blood Monocytes ◽  
Peripheral Blood Monocytes ◽  
Lymphocyte Antigen ◽  
Antigen Complex

Abstract Cerebrovascular disease (CVD) of both large and small cerebral vessels occurs in one-third of patients with sickle cell anemia (SCA) by age 20 years. Large vessel stenosis (LVS) occurs in ~10% of patients and is associated with overt stroke and/or (+) transcranial Doppler (TCD). Epistatic genetic modifiers are postulated to account for the significant phenotypic heterogeneity of SCA and likely contribute to CVD. Potential genetic modifers of CVD may be found in pathways for inflammation, adhesion, stress/immune reactions, angiogenesis, thrombosis, and oxidant generation. Peripheral blood monocytes are activated in SCA and contribute to inflammation and endothelial activation. The goal of this study is to determine if there is a difference in gene expression profiles of monocytes in patients with SCA and LVS, compared to SCA controls without CVD, and to normal African American (AA) controls. The study group consisted of 1) SCA patients with LVS [n = 6, (moyamoya = 3, no moyamoya =3)], 2) SCA patients without CVD and nornal TCD (n = 3), and 3) normal AA controls (n = 3). The 6 SCA-LVS patients were on chronic transfusion programs to maintain Hb S <30%. Monocytes were isolated by negative selection (RosetteSep Antibody) and total RNA extracted, converted to cRNA and hybridized to Affymetrix U133A GeneChip. Gene profiles were analyzed using dChip version 1.3 and gene lists were created for genes with a 2-fold or greater increase or decrease in expression with a Welch t-test p-values of 0.05 or less. Results: 1) SCA controls without CVD compared to AA controls revealed 50 differentially expressed genes (p<0.05), 16 with 2-fold or greater change. Differential gene expression was observed in pathways for angiogenesis (PD-ECGF, 5.1 fold, p = 0.025), cell signaling (lymphocyte antigen complex 6, 10.4 fold, p = 0.032, STAT1, 5.1 fold, p = 0.039), and inflammation (MARCO, 3.1 fold, p = 0.042). 2) SCA patients with LVS compared to SCA controls revealed 47 differentially expressed genes (p = <0.05) but only 6 genes with 2-fold or greater change. These included angiogenesis (PD-ECFG, -3.59 fold, p = 0.02), cell signaling (lymphocyte antigen complex 6, −4.61 fold, p = 0.02), adhesion (junction plakoglobin, −7.73 fold, p = 0.03), inflammation (LTA4H, 2.57 fold, p =0.009). These data suggest that patients with SCA and LVS overexpress leukotriene A4 hydrolase (LTA4H), an enzyme that catalyzes the final step in the leukotriene B4 (LTB4) pathway. LTB4 is a chemoattractant which triggers adhesion and aggregation of leukocytes to the endothelium. Five-lipoxygenase-activating protein (FLAP), a leukotriene pathway protein has recently been identified as a candidate gene for stroke and AMI risk in an Icelandic population. Also of interest, the SCA-LVS patients showed decreased expression of PD-ECFG and lymphocyte antigen complex 6, both genes being significantly overexpressed in SCA controls. Since the SCA-LVS patients are on chronic transfusion, underexpression could be due to the ameliorating effects of transfusion therapy. Validation studies of these findings are currently underway.

Gene Expression Profiles Document That Recently- and Previously-Divided CLL Fractions Represent a Continuum but Suggest Differing Modes of Activation for These Fractions in U-CLL and M-CLL

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 317-317
Author(s):  
Xiao J. Yan ◽  
Wentian Li ◽  
Sophia Yancopoulos ◽  
Igor Dozmorov ◽  
Carlo Calissano ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Death ◽  
Cell Signaling ◽  
Lymphoid Tissue ◽  
Research Funding ◽  
Expression Profiles ◽  
Lymphocytic Leukemia ◽  
Gene Set Enrichment Analysis ◽  
P Value ◽  
Gene Sets

Abstract Abstract 317 By using reciprocal densities of surface membrane CXCR4 and CD5, chronic lymphocytic leukemia (CLL) B cells can be divided into 3 fractions indicating time since last division (proliferative, intermediate, and resting). It has been suggested that cells in these fractions represent a continuum from resting to intermediate to proliferative. In this study, we made intraclonal gene expression profile (GEP) comparisons of these fractions from 17 CLL patients to try to confirm this notion and interclonal comparisons between U-CLL and M-CLL patients to determine if pathways involved in the actions of these fractions differed between patient subgroups. PBMCs from 8 U-CLL and 9 M-CLL patients were sorted into 3 fractions (CD19+CD3−CD5hiCXCR4lo, PROLIF), (CD19+CD3−CD5intCXCR4int, INTERM), and (CD19+CD3−CD5loCXCR4hi, REST); RNA was purified from each, and gene expression microarrays using Illumina HumanHT12 beadchips performed. To determine differentially expressed genes in intraclonal comparisons, expression value ratios for fractions from each patient were computed, log-transformed, and Student t-test performed using R (www.r-project.org); for interclonal comparisons, raw GEP data between subpopulations were compared: U-PROLIF and M-PROLIF, and U-REST and M-REST. Sets of significant genes (≥1.5 fold change and P<0.01) were analyzed using Ingenuity Pathway Analysis (IPA) and Gene Set Enrichment Analysis (GSEA). Upon plotting intraclonal average log ratios of PROLIF/INTERM vs INTERM/REST, it was clear that gene expression levels changed in the same direction, i.e. PROLIF>INTERM>REST, or PROLIF<INTERM<REST, consistent with a continuum between the 3 fractions. Within this pattern, 36 genes were significant for both plotted ratios. Of these, 29 were overexpressed, along with CD5; CD68, ITGAX, CCND2, CRIP1 and LGALS1 were the highest. Functional analysis using IPA showed these genes to be related to NFkB signaling and cell trafficking. Seven genes (ADARB1, BACH2, CNTNAP2, HRK, RHPN2, PRPML, and RXPA) were significantly downregulated, along with CXCR4. Next we characterized GEP differences between the PROLIF and REST fractions, identifying 390 genes up-regulated in PROLIF and 244 in REST. The top 5 upregulated PROLIF genes were CD68, LY96, ITGAX, CCND2 and CRIP1, and the top 5 REST genes were BACH2, CXCR4, ADARB1, RHPN2 and HRK. Functionally, the upregulated PROLIF genes were related to BCR signaling, cytokines (IFNa, IL12), NFkB, and Akt, whereas the upregulated REST genes related to BCL2, cell death and cell movement. By GSEA, 813/881 gene sets, defined by expression neighborhoods centered on cancer associated genes, were upregulated in the PROLIF with 436 gene sets significant at a false discovery rate (FDR) <10%; 206 sets were significantly enriched with p value <0.01. For the REST, 68/881 gene sets were upregulated, with none significant even at FDR <25%. Finally, we examined PROLIF and REST fractions from U-CLL vs M-CLL patients. In this interclonal analysis, 93 genes were significantly different between U-PROLIF and M-PROLIF. The top 5 in U-PROLIF were MSI2, TGFBR3, TP53I3, RGCC and IGSF3, and the top 5 in M-PROLIF were MTSS1, BACE2, BRI3BP, AP3B1 and UBE2G2. Similarly, there were 125 genes that were significantly different between U-REST and M-REST. The top 5 in U-REST were DUSP26, CLEC2B, MDK, and EGR2 and in M-REST were NAPSA, RAB24, TARDBP, KCNN4 and ADD3. Interestingly, U-PROLIF and M-PROLIF differed in pathway assignments, with upregulated genes in U-PROLIF contributing to cell signaling and activation, particularly implicating Akt, ERK and P38MAPK. The intraclonal gene GEP analysis on these 3 fractions confirms that CLL clones contain a spectrum of cells that transition in a sequential manner from PROLIF to INTERM to REST fractions. Functional analyses show that genes upregulated in PROLIF correlate with cell signaling and proliferation, while genes upregulated in REST relate to cell death. Thus the PROLIF fraction is enriched in recently divided cells that likely exit from lymphoid tissue and the REST in older, less vital cells that either traffic to lymphoid tissue or die. The interclonal analysis implies that the stimuli and/or the responses of cells in the PROLIF and REST fractions differ between U-CLL and M-CLL. This last novel finding suggests either distinct cells of origin or distinct activation pathways for the IGHV-defined CLL subsets. Disclosures: Barrientos: gilead and pharmacyclics research funding: Research Funding.

scholarly journals Rapid effects of LH on gene expression in the mural granulosa cells of mouse periovulatory follicles

Reproduction ◽  
2009 ◽  
Vol 137 (5) ◽  
pp. 843-855 ◽  
Author(s):  
Martha Z Carletti ◽  
Lane K Christenson
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Cell Signaling ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Egf Receptor ◽  
Cell Function ◽  
Early Response ◽  
Cell Gene Expression

LH acts on periovulatory granulosa cells by activating the PKA pathway as well as other cell signaling cascades to increase the transcription of specific genes necessary for ovulation and luteinization. Collectively, these cell signaling responses occur rapidly (within minutes); however, presently no high throughput studies have reported changes before 4 h after the LH surge. To identify early response genes that are likely critical for initiation of ovulation and luteinization, mouse granulosa cells were collected before and 1 h after hCG. Fifty-seven gene transcripts were significantly (P<0.05) upregulated and three downregulated following hCG. Twenty-four of these transcripts were known to be expressed after the LH/hCG surge at later time points, while 36 were unknown to be expressed by periovulatory granulosa cells. Temporal expression of several transcripts, including the transcription factorsNr4a1,Nr4a2,Egr1,Egr2,Btg1, andBtg2, and the epidermal growth factor (EGF)-like ligandsAregandEreg, were analyzed by quantitative RT-PCR, and their putative roles in granulosa cell function are discussed. Epigen (Epgn), another member of the family of EGF-like ligands was identified for the first time in granulosa cells as rapidly induced by LH/hCG. We demonstrate thatEpgninitiates cumulus expansion, similar to the other EGF-receptor ligandsAregandEreg. These studies illustrate that a number of changes in gene expression occurin vivoin response to LH, and that many of the differentially expressed genes are transcription factors that we would predict in turn modulate granulosa cell gene expression to ultimately impact the processes of ovulation and luteinization.

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